Oncolytic Viral Therapy for Cervical and Ovarian Cancer Cells by Sindbis Virus AR339 Strain

Unno, Youichi; Shino, Yuji; Kondo, Fukuo; Igarashi, Natsuhiko; Wang, Gang; Shimura, Ryuhi; Yamaguchi, Taketo; Asano, Tomohiko; Saisho, Hiromitsu; Sekiya, Souei; Shirasawa, Hiroshi

doi:10.1158/1078-0432.ccr-04-2610

Cited by 66 publications

(48 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4,5 The range of viruses showing promise as oncolytic therapies for ovarian cancer is quite broad and includes reovirus, Newcastle Disease virus, echovirus Type I, Sindbis virus, mumps virus and engineered adenoviruses. [6][7][8][9][10][11][12][13] We previously reported that a genetically modified measles virus expressing a soluble marker peptide (MV-CEA) is a potent and selective oncolytic agent, with promising activity in preclinical models of ovarian cancer. 14 MV-CEA targets and causes extensive fusion in ovarian cancer cells through the CD46 receptor, which is expressed at high levels by many tumor types, including ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of oncolytic measles virotherapy: eventual equilibrium between virus and tumor in an ovarian cancer xenograft model

Hadac

et al. 2006

Cancer Gene Ther

View full text Add to dashboard Cite

Because of their ability to replicate, the dose-response relationships of oncolytic viruses cannot easily be predicted. To better understand the pharmacokinetics of virotherapy in relation to viral dose and schedule, we administered MV-CEA intraperitoneally in an orthotopic mouse model of ovarian cancer. MV-CEA is an attenuated oncolytic measles virus engineered to express soluble human carcinoembryonic antigen (CEA), and the virus is currently undergoing phase I clinical testing in patients with ovarian cancer. Plasma CEA levels correlate with numbers of virus-infected tumor cells at a given time, and were used as a surrogate to monitor the profiles of viral gene expression over time. The antineoplastic activity of single-or multiple-dose MV-CEA was apparent over a wide range of virus doses (10 3 -10 8 TCID 50 ), with little reduction in observed antitumor efficacy, even at the lowest tested dose. However, analysis of CEA profiles of treated mice was highly informative, illustrating the variability in virus kinetics at different dose levels. The highest doses of virus were associated with higher initial levels of tumor cell killing, but the final outcome of MV-CEA therapy at all dose levels was a partial equilibrium between virus and tumor, resulting in significant slowing of tumor growth and enhanced survival of the mice.

show abstract

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of oncolytic measles virotherapy: eventual equilibrium between virus and tumor in an ovarian cancer xenograft model

Hadac

et al. 2006

Cancer Gene Ther

View full text Add to dashboard Cite

show abstract

“…Recently, a replication-defective SIN viral vector was developed as a gene therapy vector for transient and high-level expression of heterologous genes (Tseng et al, 2004). However, replication-competent wildtype SIN has an additional favourable feature for a modality of cancer therapy (Unno et al, 2005). Replication-competent oncolytic viruses, like SIN used in this study, would not follow a simple dose -response curve.…”

Section: Discussionmentioning

confidence: 99%

“…Sindbis virus (SIN) is an RNA virus belonging to the Alphavirus genus in the Togaviridae virus family; it is transmitted to birds and mammals by mosquito bites (Jan and Griffin, 1999) and subsequently spreads throughout the body through the bloodstream (Tseng et al, 2002;Unno et al, 2005). It has the potential to induce apoptosis of infected mammalian cells (Jan and Griffin, 1999;Moriishi et al, 2002).…”

mentioning

confidence: 99%

“…Sindbis virus infection induces no or only mild symptoms (fever, rash, and arthralgia) in humans (Jan and Griffin, 1999). Several replication-defective SIN vector systems have been studied for in vitro gene transfer into mammalian cells and in vivo gene therapy (Tseng et al, 2002;Yamanaka, 2004;Unno et al, 2005). However, whether replication-competent wild-type SIN can be used as an anti-cancer agent in oral cancers has not been investigated.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Oncolytic activity of Sindbis virus in human oral squamous carcinoma cells

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: Sindbis virus (SIN) infection causes no or only mild symptoms (fever, rash, and arthralgia) in humans. However, SIN has a strong cytopathic effect (CPE) on various cancer cells. This study focuses on the oncolytic activity of SIN AR399 on oral cancer cells compared with reovirus, a well-known oncolytic virus that targets cancer cells. METHODS: We analysed the cytotoxicity and growth of SIN in 13 oral squamous cell carcinoma (OSCC) cell lines (HSC-2, HSC-3, HSC-4, Ca9-22, H-1, Sa-3, KON, KOSC-2, OK-92, HO-1-N1, SCC-4, SAT, SKN-3) and normal human oral keratinocytes (NHOKs). RESULTS: Sindbis virus infection induced CPE in 12 OSCC cell lines at a low multiplicity of infection (MOI) of 0.01, but not in the OSCC cell line, HSC-4 or NHOKs. Sindbis viral growth was not observed in NHOKs, whereas high SIN growth was observed in all OSCC cell lines, including HCS-4. The cytotoxicity and growth of SIN was the same as reovirus at an MOI of 20 in 12 OSCC cell lines. The CPE was shown, by terminal deoxyribonucleotidyl transferase -mediated dUTP nick-end labelling assays, to be apoptotic cell death. Furthermore, quantitative RT-PCR of mRNA in HSC-3 and HSC-4 cells after SIN infection showed that activation of caspases, cytochrome c, and IkBa was associated with SIN-induced apoptosis. CONCLUSION: As a replication-competent oncolytic virus, SIN may be a useful therapeutic modality for oral cancers.

show abstract

“…[6] There are increasing demands for anticancer therapy. [7] In vitro cytotoxicity testing procedures reduce the use of laboratory animals, [8] and hence use of cultured tissues, and cells have increased. [9] The discovery and identification of new antitumor drug with low side effects on the immune system have become an essential goal in many studies of immunotherapy.…”

mentioning

confidence: 99%

Untitled

Jain

2017

AJP

View full text Add to dashboard Cite

Background: The goal of the present investigation was to evaluate docetaxel (DOC)-loaded gelatin nanoparticles for cancer therapy. Materials and Methods: DOC-loaded gelatin nanoparticles using ultraviolet-visible spectroscopy, X-ray diffraction, particle size and size distribution, scanning electron microscopy, drug entrapment efficiency, infrared, and in vitro drug release were characterized. The viability of MCF-7 breast cancer (BC) cells was determined by MTT. Cell sensitivity to drugs and growth curves were measured by MTT assay. Changes of cell morphology and ultrastructure were examined by optical and electron microscopy. Results: Solubility, crystallinity, and the crystal properties of an active pharmaceutical ingredient play a critical role in the value chain of pharmaceutical development, manufacturing, and formulation. The rate of drug release for formulation stored at 45°C ± 1°C was increased as compared with the fresh formulation; it might be due to the formation of more pores in the nanoparticles due to evaporation of residual amount of solvent. The in vitro release studies of drug-loaded nanoparticles were conducted at 37 ± 0.5 and 100 rpm using phosphate buffer pH 7.4 (900 ml) in a USP dissolution apparatus under sink condition. DOC-loaded gelatin nanoparticles depleted the viability of MCF human breast cell line. In this study, MCF BC cell line revealed growth inhibition in a dose-dependent manner when treated DOC-loaded gelatin nanoparticles at concentrations ranging from 5 to 100 µg. Conclusion: The DOC-loaded gelatin nanoparticles displayed differential cytotoxicity toward MCF7 cancer cells. These biogenic nanoparticles are biocompatible and found to be good candidates for sustained drug delivery in diseases like cancer.

show abstract

Oncolytic Viral Therapy for Cervical and Ovarian Cancer Cells by Sindbis Virus AR339 Strain

Cited by 66 publications

References 25 publications

Pharmacokinetics of oncolytic measles virotherapy: eventual equilibrium between virus and tumor in an ovarian cancer xenograft model

Pharmacokinetics of oncolytic measles virotherapy: eventual equilibrium between virus and tumor in an ovarian cancer xenograft model

Oncolytic activity of Sindbis virus in human oral squamous carcinoma cells

Untitled

Contact Info

Product

Resources

About